Elution of cell-bound anti-prostatic epithelial antibodies after multiple cryotherapy of carcinoma of the prostate

Antibodies reactive with the cytoplasmic membrane or intercellular areas of autologous human and monkey prostatic secretory epithelial cells have been demonstrated by immunofluorescence in an eluate prepared from prostatic tissue obtained from a patient with metastatic adenocarcinoma of the prostate (CaP) after multiple cryotherapy of his primary prostatic tumour. While limited to the study of one patient, elution of anti-prostatic antibodies offers further documentation to previous studies pointing toward the participation of immunologic processes in CaP.     

IKKalpha at the crossroads of inflammation and metastasis

The development of solid tumors is regulated by dynamic interactions between evolving neoplastic cells and their microenvironment. Luo et al. (2007) recently demonstrated that tumor-infiltrating immune cells expressing RANKL induce activation and nuclear localization of IKKalpha in prostatic epithelial tumor cells. This leads to repression of maspin, a critical suppressor of metastasis, and thus commits malignant prostatic epithelial cells to a metastatic fate.     

Cytology and immunocytochemistry of bilateral breast metastases from prostatic cancer. Report of a case

The cytologic findings in fine needle aspirates of a previously treated prostatic cancer metastatic to both breasts in a 65-year-old man are described. The prostatic origin of the poorly differentiated adenocarcinoma cells was demonstrated by identification of cytoplasmic prostate-specific antigen. The clinical importance of a conclusive diagnosis differentiating a primary from a metastatic lesion is discussed; this case illustrates the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis in making such determinations.     

Fine needle aspiration cytology of a metastatic duct carcinoma of the prostate: a case report

BACKGROUND: Prostatic ductal carcinoma (PDC) is a rare variant of prostatic adenocarcinoma. Without proper clinical information, a fine needle aspiration (FNA) diagnosis of metastatic PDC can be challenging as this tumor can morphologically mimic adenocarcinomas from other sites. To our knowledge, FNA findings of metastatic PDC have not been previously reported. CASE: An 85-year-old man presented with a large, destructive pelvic bone lesion with soft tissue extension. He had undergone a prostatectomy 30 years earlier for "benign prostatic hypertrophy" but had no known history of malignancy. The aspirates were hypercellular and composed of numerous monolayered or folded cohesive sheets of tumor cells with minimal cytologic atypia. The tumor cells had abundant, clear cytoplasm, evenly spaced nuclei, finely granular chromatin, inconspicuous nucleoli and occasional mitotic figures. The background was clean and contained a few wisps of thin mucin. Cell block sections revealed tumor cells forming tubulopapillary architecture lined with tall columnar cells with focal nuclear pseudostratification, reminiscent of uterine endometrial carcinoma. Positive immunoreactivity for prostate-specific antigen and prostatic acid phosphatase confirmed the tumor's prostatic origin. CONCLUSION: Because of the rarity and nonspecific cytomorphologic characteristics of this tumor, clinical history, radiologic findings and a high index of suspicion in conjunction with ancillary studies are important in achieving a correct FNA diagnosis of metastatic PDC.     

Prostate carcinoma metastatic to the skin as an extrammamary Paget¿s disease

ABSTRACT: AimThe current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified.Discussion and conclusionsWe review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276.     

Clonal variation in the impact of ethyl methanesulfonate and 5-azacytidine on the metastatic phenotype of human prostatic tumor cells in athymic nude mice

Parallel in vitro exposure to 5-azacytidine or to ethyl methanesulfonate either significantly reduced or had no major impact on the experimental metastasis capacity of different clones of the human prostatic carcinoma subline 1-LN-PC-3-1A. The impact of these agents on metastatic capacity varied (1) among different clones and (2) between clones and the uncloned parental line. Analysis of the process by which these agents modify the metastatic phenotype of human tumor cells may offer insight into the process of phenotypic diversification.     

Prostatic acid phosphatase immunoperoxidase staining of cytologically positive effusions associated with adenocarcinomas of the prostate and neoplasms of undetermined origin

An immunoperoxidase staining technique was employed in an effort to demonstrate prostatic acid phosphatase in sections of the effusion cell blocks in a retrospective investigation of the incidence of malignant prostatic cells in body cavity effusions in 33 patients with histologically confirmed prostatic cancer. An attempt was also made to identify the prostate as a possible anatomic site of origin in 26 patients with an unknown primary but with cytologically positive fluids. Neoplastic cells were identified in the effusion specimens in 21.2% of the patients with confirmed prostatic cancer; the sources, however, were either primary or metastatic carcinomas of nonprostatic origin. None of the cytologic specimens in this study demonstrated a positive prostate-specific acid phosphatase staining reaction, as did the prostatic metastases to the lungs used as controls.     

Real-time impedance assay to follow the invasive activities of metastatic cells in culture

Here we present research detecting the invasive activities of metastatic cells in vitro using electric cell-substrate impedance sensing (ECIS). The assay is based on previous microscopic observations, where metastatic cells added over established endothelial cell layers were observed to attach to and invade the cell layer. Human umbilical vein endothelial cells (HUVECs) werefirst grown to confluence on small gold electrodes. The impedance of these electrodes was followed after the addition of suspensions of different sublines of the Dunning murine prostatic adenocarcinoma series (G, AT1, AT2, AT3, ML, and MLL). For highly metastatic sublines, within an hour after being challenged, the impedance of the confluent HUVEC layer was substantially reduced. The effect of the weakly metastatic sublines was less pronounced, and the extent and the rate of this drop in impedance could be correlated with the metastatic potential of each of six sublines tested. The real-time assay is effective in both normal and low (1%) serum concentrations, and the detected activity requires the presence of viable transformed cells. In addition to the murine cell lines, similar behavior was observed using four established human prostatic cancer lines (DU145, PC3, TSU, and PPC1). These results suggest that this ECIS-based assay might be used with primary human cultures to establish the metastatic abilities of cells isolated from biopsies.     

Récidive testiculaire isolée d’un adénocarcinome prostatique révélée par TEP/TDM 18F-fluorocholine

With the development of new PET tracers, nuclear medicine has become a central element in the search for prostate cancer recurrence. A 75-year-old patient followed for a prostate adenocarcinoma was referred to our center for biological recurrence, with a gradual rise of prostatic specific antigen (PSA). A pelvic MRI and ¹⁸F-fluorocholine PET/CT were performed, both showing no strong evidence of local recurrence. This last examination however revealed an intense pathological radiotracer uptake only in the left testicle. After performing a complementary ultrasound imaging, orchiectomy revealed a metastatic testicular localization of the prostatic adenocarcinoma. PSA control after surgery had normalized. This case emphasizes one of the unusual presentations of metastatic prostatic disease to be aware of.     

MiR-203 controls proliferation,migration and invasive potential of prostate cancer cell lines

Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue, and in metastatic prostate cancer cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer.     

Gene targeting to the stroma of the prostate and bone

Abstract Stromal–epithelial interactions mediated by paracrine signaling mechanisms dictate prostate development and progression of prostate cancer. The regulatory role of androgens in both the prostate stromal and epithelial compartments set the prostate apart from many other organs and tissues with regard to gene targeting. The identification of androgen-dependent prostate epithelial promoters has allowed successful gene targeting to the prostate epithelial compartment. Currently, there are no transgenic mouse models available to specifically alter gene expression within the prostate stromal compartment. As a primary metastatic site for prostate cancer is bone, the functional dissection of the bone stromal compartment is important for understanding stromal–epithelial interactions associated with metastatic tumor growth. Use of currently available methodologies for the expression or deletion of gene expression in recent research studies has advanced our understanding of the stroma. However, the complexity of stromal heterogeneity within the prostate remains a challenge to obtaining compartment or cell-lineage-specific in vivo models necessary for furthering our understanding of prostatic developmental, benign, tumorigenic, and metastatic growth.     

Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cell lines and tissues with malignant progression.

Ectopical expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the development and malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. We cloned and characterized the human MUC18 (huMUC18) cDNA gene from three human prostate cancer cell lines and three human melanoma cell lines. The cDNA sequences from the six human cancer cell lines were identical except differences in one to five nucleotides. The deduced amino acid sequences of the longest ORF were 646 amino acids that were identical in these cDNAs except for one to three amino acid residues. The amino acid sequences of all our huMUC18 cDNA genes are similar to that cloned by other group (GenBank access #M28882) except differences in the same seven amino acids. We conclude that huMUC18 cDNA gene reported here represents the gene product from a major allele. The MUC18 mRNA and protein was expressed in three metastatic prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one non-metastatic prostate cancer cell line (LNCaP.FGC). The expression of huMUC18 in these four cell lines is positively related to their extent of in vitro motility and invasiveness and in vivo metastasis in nude mice. HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from cultured primary normal prostatic epithelial cells and the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas, and in cells of a perineural invasion, a lymph node, and a lung metastases compared to that in normal or benign hyperplastic epithelium (BPH). We therefore conclude that MUC18 expression is increased during prostate cancer initiation (high grade PIN) and progression to carcinoma, and in metastatic cell lines and metastatic carcinoma. Increased expression of MUC18 is implicated to play an important role in developing and malignant progression of human prostate cancer. Furthermore, the lacking of predominant cytoplasmic membrane expression of MUC18 appeared to correlate with malignant progression of prostate cancer.     

Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines.

Metastatic variants of human prostatic adenocarcinoma cell lines (DU-145, LNCaP, and ND-1) were studied by using soft agar colony forming efficiency, nude mice tumorigenicity, in vitro invasion assay, and type IV collagenase assay. The DU-145 and ND-1 cell line showed higher metastatic potential than LNCaP. Lipids from DU-145, ND-1, and LNCaP cells were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. The major lipids were phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, fatty acids, and cholesterol. The sphingomyelin level was significantly higher in highly metastatic cells (DU-145 and ND-1) compared with the lower metastatic variant (LNCaP). The increase in the synthetic pathway and decrease in degradation pathway of sphingomyelin in microsomal fractions was sufficient to account for the measured increase in sphingomyelin in DU-145 cells compared with LNCaP cells. The major fatty acids of these lipids were palmitic (16:0), stearic (18:0), oelic (18:1), and arachidonic acid (20:4). The arachidonic acid level was significantly decreased in DU-145 and ND-1 compared with LNCaP cells. Electron microscopic studies showed no significant changes in the morphology of DU-145, ND-1, and LNCaP cells. The results of these investigations demonstrate for the first time that sphingomyelin and arachidonic acid contents are different in high and low metastatic variants of human prostatic adenocarcinoma cell lines.     

Fine needle aspiration diagnosis of transitional cell carcinoma metastatic to the brain. A case report

BACKGROUND: Transitional cell carcinoma (TCC) rarely metastasizes to the brain. In this case, aspiration of a cystic brain lesion was performed and a cytologic diagnosis made. To the best of our knowledge, this is the first reported case of TCC metastatic to the brain diagnosed by fine needle aspiration. CASE: A 72-year-old male with a past medical history of invasive TCC, colonic adenocarcinoma and prostatic adenocarcinoma presented with a large, right, temporal, cystic mass. Fine needle aspiration was performed intraoperatively, and a cytologic diagnosis of metastatic TCC was rendered and confirmed by subsequent tissue examination. CONCLUSION: Intraoperative fine needle aspiration of cystic tumors can be useful in identifying the primary site. The cytologic features of intracerebral metastatic TCC can differ significantly from those observed in urinary tract specimens of high grade TCC. A predominance of large fragments of malignant cells with numerous mitotic figures and apoptotic bodies was seen in the former. The background showed high grade, single transitional cells similar to those observed in urinary tract samples of TCC.     

On the safety assurance of cell processing carried out in medical institutions for autologous immuno-cell therapy

Recent evaluation of human prostate tissues has shown predominantly high expression of the macrophage colony-stimulating factor receptor in prostatic intra-epithelial neoplasia or prostate cancer. However, the expression of its ligand, the macrophage colony-stimulating factor (M-CSF), and the biological role of this signaling in prostate cancer has not been analyzed. In this research we determined the relationship of serum M-CSF level to clinical parameters of prostate cancer progression. We measured the serum level of M-CSF in 170 patients with histologically confirmed prostatic adenocarcinoma and in 54 patients in whom prostate cancer was not detected. We also investigated the M-CSF expression in prostate cancer tissues by immunohistochemistry. The serum levels of M-CSF in bone metastatic prostate cancer patients was significantly higher than those in non-metastatic patients, while M-CSF did not differ with regards to histological grade, Gleason score or local tumor progression. M-CSF expression was detected in prostate cancer cells themselves by immunohistochemistry. These results suggest that M-CSF may have a functional role in prostate cancer progression.     

Tetrodotoxin suppresses morphological enhancement of the metastatic MAT-LyLu rat prostate cancer cell line

Voltage-gated Na⁺ channels are expressed by highly metastatic MAT-LyLu cells, but not by poorly metastatic AT-2 cells, derived from the rodent Dunning model of prostatic cancer. We have investigated the possible involvement of these channels in the morphological development of the cells. Incubation of both the MAT-LyLu and the AT-2 cell line for 24 h with the Na⁺ channel blocker tetrodotoxin (TTX) at 6 μM altered the morphology only of the MAT-LyLu cell line. TTX produced significant decreases in: (a) cell process length and (b) field diameter, and increases in (c) cell body diameter and (d) process thickness. Importantly, 6 μM TTX had no significant effects on proliferation rates or cellular toxicity. The results suggest that Na⁺ channel activity plays a significant role in determining the morphological development of MAT-LyLu cells in such a way as to enhance their metastatic potential. Received: 9 March 1998 / Accepted: 5 October 1998     

Glycophenotype of prostatic carcinomas

The factors that affect the progression of prostatic carcinoma are poorly understood, but it is known that carbohydrate antigens on the tumour cell surface play a role in the transforming and metastatic processes. The present report aimed to perform a comparative, lectin-histochemical study of benign and carcinomatous prostates, using a battery of lectins, in combination with monoclonal antibodies against Lewis antigens, and a semi quantitative study, to investigate the changes in glycosylation patterns that occur in prostatic carcinoma. Blocks from 27 necropsy cases of prostatic carcinoma were sectioned and stained with H+E, fifteen biotinylated lectins chosen to probe for a wide range of oligosaccharide sequences within several categories of glycoprotein glycans, using a lectin-biotin avidin-peroxidase method, and monoclonal antibodies against Lewisa, sialyl Lewisa and sialyl Lewisx antigens. The glycophenotype of prostatic carcinoma differed from that of the noncancerous prostate in revealing more intense staining with the following lectins (AAA, UEA-1, DBA, WFA, VVA, HPA, BSA-1B4, MPA, ECA, AHA, and CTA), while the binding patterns of (GNA and NPA) were almost similar in both prostatic carcinoma and the noncancerous prostate. Lewis antigens are found to be expressed in prostatic carcinomas but not in the noncancerous prostate. The observations of this study suggest that the gylcophenotype of transformed prostatic cells was modified. It showed a moderate increase in, and changing patterns of, fucosylation and galactosylation, increased branching of side chains and sharp rise in 2 deoxy, 2 acetamido galactosylation and masking process by sialylation, especially by α2-3 and α2-6 linkages. All these changes in the glycosylation pattern of the transformed prostatic cells were observed on O-glycans, no changes were observed on N-glycans.     

Equivocal test results and prognostic staging uncertainties in the evaluation of patients with cancer of the prostate

In the staging of cancer, equivocal test results may occur in subjectively evaluated imaging procedures whose interpretations raise the possibility of metastases but are too uncertain to rule in or rule out metastatic spread, and in tests whose repetitions in the same patient yield conflicting results about dissemination. We assessed the frequency and prognostic correlates of test results giving equivocal evidence of disseminated (Stage IV) disease in an inception cohort of 280 patients receiving initial treatment for prostatic cancer between 1973-76. Among tests used for clinical staging, lymphangiograms (equivocal in 28 percent of tested patients), bone scans (equivocal in 25 percent of tested patients), and bone radiographs (equivocal in 20 percent of tested patients) most frequently yielded interpretations that equivocally suggested metastatic spread. Eighty-three (45 percent) of the 185 patients without clear-cut dissemination (Stages I-III) had at least one equivocal test result that suggested dissemination and that remained unresolved at the time of selection of therapy. Five-year survival (30 percent) for the 20 patients with local extracapsular spread (Stage III) and multiple equivocal results suggesting dissemination was identical to that for patients with clear-cut dissemination. In contrast, other patients with equivocal dissemination in Stages I-III had survival rates similar to those patients in the same stage and lacking equivocal dissemination. Unresolved equivocal staging results frequently complicate management decisions for patients with prostatic cancer. Survival analyses aid these decisions by demonstrating that equivocal findings of dissemination are prognostically unimportant unless they are multiple and occur in the context of unequivocal extracapsular spread.     

Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer

The regulation of intracellular Ca(2+) plays a key role in the development and growth of cells. Here we report the cloning and functional expression of a highly calcium-selective channel localized on the human chromosome 7. The sequence of the new channel is structurally related to the gene product of the CaT1 protein cloned from rat duodenum and is therefore called CaT-like (CaT-L). CaT-L is expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but is undetectable in healthy prostate tissue and benign prostatic hyperplasia. Additionally, CaT-L is expressed in normal placenta, exocrine pancreas, and salivary glands. New markers with well defined biological function that correlate with aberrant cell growth are needed for the molecular staging of cancer and to predict the clinical outcome. The human CaT-L channel represents a marker for prostate cancer progression and may serve as a target for therapeutic strategies.